Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group.
OBJECTIVE
To evaluate the efficacy and safety of a GnRH agonist, leuprolide acetate depot, alone and in combination with three hormonal add-back regimens in the management of endometriosis-associated pelvic pain.


METHODS
Two hundred and one patients were enrolled in this multicenter, randomized, double-blind, 1-year trial. All patients were given an intramuscular injection of leuprolide acetate depot 3.75 mg every 4 weeks. Patients were assigned to one of four treatment groups: Group A received placebos for progestin and estrogen, group B received norethindrone acetate 5 mg daily and placebo for estrogen, group C received norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg daily, and group D received norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg daily. Pelvic pain scores were assessed monthly, and bone density was measured after 24 and 52 weeks.


RESULTS
By week 8, all four groups showed significant improvement in pelvic pain scores compared with baseline levels. A higher proportion of group D patients terminated the study prematurely due to a lack of improvement in symptoms. Group A experienced a 6.3 +/- 2.3% (P < or = .001) loss in bone density after 52 weeks of treatment, whereas bone density was preserved in all three add-back groups.


CONCLUSIONS
The use of leuprolide acetate depot in combination with norethindrone acetate 5 mg alone, or with norethindrone acetate and conjugated equine estrogens 0.625 mg, provides effective suppression of pelvic pain symptoms associated with endometriosis while protecting against bone loss.
Hornstein
M D
MD
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. mdhornstei@bics.bwh.harvard.edu
Surrey
E S
ES
Weisberg
G W
GW
Casino
L A
LA
D000328:Adult; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004715:Endometriosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004857:Equilin / Q000008:administration & dosage; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007273:Injections, Intramuscular; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000502:physiology; D009640:Norethindrone / Q000008:administration & dosage; D010147:Pain Measurement / Q000706:statistics & numerical data; D010352:Patient Dropouts / Q000706:statistics & numerical data; D017699:Pelvic Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D045167:Progesterone Congeners / Q000008:administration & dosage; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
D003692:Delayed-Action Preparations; D008055:Lipids; D045167:Progesterone Congeners; D004857:Equilin; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016729:Leuprolide; D009640:Norethindrone